Urogenital or anorectal transmucosal vaccine delivery system

ABSTRACT

The invention is directed to a suppository based vaccine delivery system for immunizing against urogenital and anorectally transmitted infectious disease in humans and animals and a method for treating the same. More particularly, this invention is directed to a suppository based vaccine delivery system for the prophylaxis against or treatment of urogenital or anorectal transmitted infectious diseases, such as from viral or microbial pathogens. The suppository based delivery system comprises vaccine and/or vaccine adjuvant(s) comprised of whole or fractionated viral or other microbial pathogens, or their purified cellular constituents, whether native, mutated, synthetic, cloned or recombinantly expressed, that consists of nucleic acids, proteins, lipids or other antigenic determinants capable of producing humoral or cellular-mediated immunity in humans or animals; and a polyethylene glycol base; wherein the suppository is adapted to be inserted into a bodily orifice of a human or animal so as to allow the suppository to be in contact with tissue of the bodily orifice to facilitate transfer of vaccine or vaccine adjuvant(s) material therethrough.

FIELD OF INVENTION

The present invention relates generally to a system and method fortreating disease in humans and animals, specifically a prophylactictreatment of viral or microbial infections in humans or animals. Moreparticularly, the invention relates to a suppository-based, vaccinedelivery system for prophylaxis against or therapy for viral ormicrobial infections in humans or animals, wherein the suppository isintended for transmucosal immunization and is comprised of a vaccine orvaccine adjuvant(s) that is derived from whole or fractionated viral orother microbial pathogens, or their purified cellular constituents orderivatives, whether native, synthetic, cloned or recombinantlyexpressed, that consists of nucleotide sequences, proteins or otherantigenic determinants capable of producing humoral or cellular-mediatedimmunity in humans or animals. Still more particularly, the presentinvention relates to a suppository-based, vaccine delivery system forprophylaxis against or therapy for viral or microbial infections inhumans or animals, wherein the suppository is used for transmucosalimmunization and is comprised of a vaccine or vaccine adjuvant(s)intended for mucosal immunization that is derived from whole orfractionated viral or other microbial pathogens, or theirpurified-cellular constituents, whether native,synthetic, cloned orrecombinantly expressed, that consists of nucleotide sequences, proteinsor other antigenic determinants capable of producing humoral orcellular-mediated immunity in humans or animals, and wherein thesuppository is comprised of a suitable base that liquefies or becomeswater miscible at body temperature in order to deliver vaccinecomponents and/or vaccine adjuvant components to the urogenital oranorectal mucosa so as to cause or enhance the development of a desiredimmune response.

BACKGROUND OF THE INVENTION

Viral and microbial pathogens transmitted through or originating fromexposure of the urogenital or anorectal epithelium or mucosa are a majorproblem in medicine. Urogenital and anorectal structures and systemictissues beyond may be affected. Such infectious disease can result frommucosal exposure during sexual contact or other contact or fromopportunistic growth of the urogenital or anorectal flora.

A tendency for recurrence, reinfection and chronic progression ischaracteristic of many urogenital or anorectal tract infections. Viralor microbial adherence to the mucosal epithelium is frequently a keyprecondition for the colonization or infection of these tissues.In-vitro studies have shown that the adherence phenomenon is oftenaccomplished via the pili of bacteria or other outer membraneconstituents of infecting viruses or microbes. Such adherence can beprevented by the development of antibodies and/or enhancement ofcell-mediated immunity against antigenic components of the invadingorganisms, which include viruses, bacteria, protozoa, fungi and thelike.

Bacteria and viruses are the most frequent causative agents ofgenitourinary or anorectal tract infections. The genitourinary/anorectaltracts can also be infected by other microorganisms, such as protozoa,fungi and the like. Recurrence and chronicity are characteristic of manygenintourinary/anorectal tract infections. Recurrence may be due toeither relapse or reinfection.

In spite of a great deal of progress in the treatment of infectiousdisease, the morbidity and mortality of genitourinary/anorectal tractinfections remains unchanged. The reasons for this are myriad and dependon the host susceptibility, heightened sexual exposure and on viral ormicrobial factors.

Recurrences of infections with a previously infecting organism mayresult from inadequacy of the treatment administered because ofincorrect choice of medicine, emergence of resistance strains,insufficient treatment duration, insufficient concentration ofchemotherapeutic agents, the existence of bacterial L-forms, andpersistence or survival of viral or microbes in urinary calculi orepithelium of the vaginal or anorectal mucosa and surrounding tissues.Recurrent urogenital/anorectal infections can be reinfections withdifferent strains of organisms responsible for prior infections andgenerally having a greater capacity to adhere to the epithelial cells ofthe vagina, urethra or rectum. The reinfecting bacteria can originate inthe intestinal flora. Frequently, viruses and chlamydia pathogens maylay dormant in epithelial cells and revert to an active state throughmechanisms not fully understood.

The composition of the urogenital or anorectal flora may be altered bychemotherapeutic agents that are used in the treatment and prophylaxisof genitourinary or intestinal infections. The flora frequently developantibiotic resistance and cause a reinfection or primary opportunisticinfection. Such infections may be a consequence of the eradication ofnormal, harmless flora, such as lactobacilli, allowing other pathogenicmicrobes, resistant to the antibiotics, to₁₃ flourish.

Studies have revealed that low levels of secretory IgA (sIgA) in urineindicate a defective local immune response of the urinary tract andfavor urogenital tract infections. An important property of sIgA is theprevention of interaction of bacterial pili or outer membraneconstituents of viruses or other microbes with the specific receptorsfound on the epithelium of the vaginal/anorectal mucosa or urinarytract. Pili-mediated adhesiveness is an important virulence factor ofthe bacteria involved. In the case of viruses and non-piliated microbes,other outer membrane constituents are involved in host-attachmentphenomena, prior to propagation to infection. For the defense againstinfection it is important to reduce the adhesion of the pathogens to theepithelium or to prevent the attachment of the pathogen altogether.

Normally, the host organism forms specific local antibodies against theinvading bacteria and secretes these antibodies as sIgA. In patientswith persisting or frequently relapsing urinary tract infections thisnatural mechanism of local immunological infection defense is apparentlydisturbed. Therefore, enhancement of immune defense is a rational meansof eliminating the cause of recurrent urinary tract infections.

A vaccination strategy that stimulates the production of antibodies to aspectrum of antigens that are present in several types of pathogens isdesirable. Vaccination of the urogenital or anorectal epithelium withnucleic acids encoding specific proteins involved in pathogen-hostattachment phenomena presents a novel method of stimulatingcell-mediated immunity.

Previously, vaccines against urogenital infections have beenadministered parenterally or orally and have resulted in enhancedresistance to urogenital infections. However, patients suffer from sideeffects such as malaise, fever, and muscle soreness. Oral vaccines aresubject to the destructive influences of gastric acidity and digestiveenzymes. A necessary retention at a local surface for extendedtransmucosal contact may be difficult to achieve. Prior art concerningmucosal vaccination through the vaginal route using whole cell lysateshas taught enhanced resistance to recurrent infection, but there is nomention of transmucosal immunization by the anorectal route and theproduction of transmucosal immunity against local infection at the siteof delivery system target. No specifically therapeutic local immuneresponse to a delivery system is presented. The efficacy presented isconfined to non-specific vaccine materials that present a complexpotential to produce complex reactions by poorly understood mechanisms.

In an attempt to overcome the defects associated with parenteral andoral administrations of vaccines or in using vaginally-deliveredvaccines comprised of fractionated or whole cell extracts, anintravaginal or intrarectal mucosal vaccine delivery system againstinfections is proposed wherein the vaccine is comprised of purifiedantigenic determinants capable of stimulating an immune response topathogenic factors involved in attachment and disease. Administering avaccine against urogenital or anorectal infections intravaginally orintrarectally is that there is a mucosal immune system wherein antigensare absorbed through mucosal surfaces and processed by specialized locallymphoid tissues, after which antibodies are secreted onto local mucosalsurfaces. In the case of nucleotide vaccines, epithelial cells of themucosa express the proteins to the cell surface promotingcellular-mediated immune responses. As discussed above, in thegenitourinary tract, temporary or partial deficiencies in local vaginalor urinary antibodies are an important factor in the heightenedsusceptibility to urogenital infections shown in some women.Immunization-via the mucosal surfaces-within the genitourinary tract ispreferable to parental or oral routes as it has been discovered thatvaccination via the intravaginal surface creates a secretory immuneresponse in the urogenital tract. With nucleotide vaccines, suchvaccination stimulates specific cellular-mediated immune responses.

Advances in the identification of specific pathogenic factors involvedin infection attachment and propagation, the elucidation of the mucosalimmune system and the ability of the mucosal tissue to participate incellular-mediated immune response via nucleotide vaccination suggestthat vaccination of the genitourinary/anorectal tract by a transvaginalor anal route is preferable to oral or parenteral immunization. Thespecific method of vaginal or rectal immunization may actually resolveinfection before disease ensues, preventing pathogen attachment orneutralizing toxins prior to pathogen and host interaction.

For instance, in the past, urinary tract infections vaccines wereadministered vaginally in the form of a liquid vaccine. Several problemswere associated with the intravaginal administration of liquid urinarytract infections vaccine. The major problem encountered was that theliquid vaccine flowed out of the vagina soon after insertion. Thisseverely limits the amount of time that the liquid antigens are incontact with the mucosal surface of the vagina, decreasing theeffectiveness of the vaccine. The antigens need sufficient contact withthe vaginal mucous membrane to elicit a secretory immunoglobin response.Patients receiving the vaccination were required to lie in a supineposition for an extended time after receiving the vaccine to prevent thevaccine from immediately flowing out of the vagina. However, often thevaccine still leaked out of the vagina following the period of time inthe supine position, limiting the effectiveness of the vaccine. Inaddition, the requirement that patients lie in a supine position for anextended time after receiving the vaccine, is a burden on the patient.Patients may receive several vaccinations over the course of treatmentand the patients must spend a considerable amount of time after eachvaccination immobile.

U.S. Ser. No. 08/923,813 entitled Vaginal Suppository Vaccine ForUrogenital Infections was filed Sep. 4, 1997 and allowed. Thisapplication is owned by assignee herein and relates to a suppositorybased vaccine delivery system for immunizing against urogenitalinfectious diseases in humans.

It is apparent that improvements are necessary in optimizing vaccinedelivery to the urogenital mucosa for effective prophylaxis againsturogenital infectious diseases. Further, it is desirable to have arectally-administered vaccine for effective prophylaxis against rectaltract infections involving transmission through the anorectal tract.

The subject invention overcomes the above limitations and others, andteaches a suppository-based vaccine delivery system for prophylaxisagainst urogenital and anorectal tract infectious diseases, such asbacterial, protozoal, fungi, viral infections and the like, usingfractionated, whole cell or purified protein, nucleic acid or lipidconstituents, whether native, mutated, synthetic, cloned orrecombinantly expressed, of urogenital/anorectal pathogens thatstimulate the generation of humoral or cellular-mediated immuneresponse.

SUMMARY OF THE INVENTION

According to the present invention, there is provided an intravaginallyor intrarectally administered suppository based vaccine delivery systemfor prophylaxis against urogenital or anorectal localized or transmittedinfectious diseases.

Further according to the present invention, there is provided asuppository based vaccine delivery system for the prophylaxis against ortreatment of urogenitally or rectally transmitted or localizedinfectious diseases, such as bacterial, protozoal, fungal or viralinfections wherein the vaccine or vaccine adjuvant is in contact withthe vaginal or anorectal mucous membrane for a sufficient period of timeto enhance the immune response.

Still further according to the present invention, there is provided asuppository based vaccine delivery system for the prophylaxis against ortreatment of urogenitally or rectally transmitted or localizedinfectious diseases, such as bacterial, protozoal, fungal or viralinfections, wherein the vaccine or vaccine adjuvant is easilyadministered, does not require the patient to lie in a supine positionfor an extended period of time after receiving the vaccination, and issuitably administered by the patient for primary and routine boosterrequirements.

Still further according to the present invention, there is provided asuppository based vaccine delivery system for prophylaxis againsturogenitally or rectally transmitted or localized infectious diseases,such as bacterial, protozoal, fungal or viral infections in humans oranimals, said suppository comprising: a vaccine or vaccine adjuvantcontaining whole or fractionated viral or other microbial pathogens, ortheir purified cellular constituents, whether native, synthetic, clonedor recombinantly expressed, that consists of nucleic acids, proteins,lipids or other antigenic determinants capable of producing humoral- orcellular-mediated immunity in humans or animals, wherein the suppositoryis comprised of a suitable base that liquefies or becomes water miscibleat body temperature in order to deliver vaccine components to theurogenital or anorectal mucosa; wherein the suppository is adapted to beinserted vaginally or rectally so as to allow the suppository to be incontact with mucous membrane to facilitate transfer of vaccine orvaccine adjuvant material therethrough.

An advantage of the present invention is the provision of a suppositorybased vaccine delivery system for the prophylaxis against or treatmentof urogenital and/or rectally transmitted or localized infectiousdiseases, such as viral or other pathogenic microbial infections,wherein the vaccine or vaccine adjuvant is in contact with the vaginalor rectal mucous membrane for a sufficient period of time to enhance theimmune response.

Another advantage of the present invention is the provision of asuppository based vaccine delivery system wherein humoral- and/orcell-mediated stimulation from mucosal vaccination allows immuneresponses to specifically keep viral or microbial shedding orcolonization from occurring or recurring, or prohibiting pathogen-hostattachment instead of fighting the infection after it has colonized orhas propagated.

Another advantage of the present invention is the provision of asuppository based vaccine delivery system wherein the suppository can beeasily manufactured to allow incorporation of vaccine or vaccineadjuvant(s) with preservatives, such as thimersal; is a solid at orbelow room temperature for structure and to allow ease of insertion; andbecomes liquified or water-miscible at body temperature so as to allowits components to enhance an immune response.

Another advantage of the present invention is the provision of asuppository based vaccine delivery system for the prophylaxis againsturogenitally or rectally transmitted or localized infectious diseases,such as viral or other pathogenic microorganism infections, wherein thevaccine is easily administered, and does not require the patient to bein a supine position for an extended period of time after receiving thevaccination.

Another advantage of the present invention is the provision of asuppository based vaccine delivery system wherein the vaccine can bereadily self-administered by the patient.

Another advantage of the present invention is the provision of asuppository based vaccine delivery system wherein the administration ofthe vaccine is relatively painless.

Yet another advantage of the present invention is the provision of asuppository based vaccine delivery system wherein the patient mayself-administer booster vaccinations periodically. Still otheradvantages of the invention will become apparent to those skilled in theart upon a reading and understanding of the following detaileddescription, and appended claims.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

This invention is directed to a suppository based vaccine deliverysystem for immunizing against infectious disease in humans and animalsand a method for treating the same. More particularly, this invention isdirected to a suppository based vaccine delivery system for theprophylaxis against or treatment of urogenitally and anorectallylocalized or transmitted infectious diseases, such as from viral orother pathogenic microbial infections including but not limited tobacteria, protozoans, fungi and the like. The suppository based vaccinedelivery system comprises a vaccine and/or vaccine adjuvant(s)comprising pathogenic microbial or viral antigenic constituents andoptionally a preservative and optionally a buffer; wherein thesuppository is adapted to be inserted into a bodily orifice of a humanor animal so as to allow the vaccine and/or vaccine adjuvant to come incontact with the mucosal tissue of the bodily orifice to facilitatetransfer of the suppository material therethrough.

The suppository comprises a vaccine and/or vaccine adjuvant(s)comprising fractionated or whole cell or purified cellular constituentswhether native, mutated, synthetic, cloned or recombinantly-expressedpathogenic microbial or viral protein lipids or nucleic acidconstituents that are capable of stimulating humoral- orcellular-mediated immune responses against which the pathogens orconstituents correspond.

The suppository comprises a vaccine and/or vaccine adjuvant(s) that isprepared by either purifying native pathogen constituents, by synthesisor recombinant expression of protein or genetic components of nativepathogens or by purifying synthetic, mutated or cloned pathogen-derivednucleic acid sequences.

The suppository of the present invention comprises any suitablesuppository base known in the art. More particularly, the suppositorybase comprises material that is solid or semi-solid at or below roomtemperature but liquefies or becomes water-miscible at body temperature.The suppository base includes but is not limited to polyethylene glycol,triglycerides, fatty acids, fatty alcohols, glycerin and the like.Preferably the suppository base is polyethylene glycol. The suppositorybase optionally includes emulsifying agents such as polysorbate,gelatin, methylcellulose, alginic acid, sodium lauryl sulfate, and thelike.

The suppository base is present in the delivery system in any suitableamount so as to allow the incorporation of the vaccine or vaccineadjuvant(s) in a solid or semi-solid form so that the structuralintegrity is maintained or that insertion into a body orifice can beeasily performed. When inserted, the suppository base liquefies orbecomes water-miscible at body temperature so as to allow the vaccineand/or vaccine adjuvant components to become in contact with the mucousmembrane for a sufficient period of time to enhance the immune response.The weight percent of the suppository base is dependent upon the size ofthe bodily orifice of the human and/or the animal, the dosage of vaccineand/or vaccine adjuvant(s) necessary to elicit an immune response andits physiochemical characteristics that allow it to remain solid at orbelow room temperature. The suppository comprises from about 50% togreater than 99%, preferably about 75% to greater than 99% by weight ofthe suppository base. Preferably the suppository comprises about 75% toabout 98% by weight polyethylene glycol. Preferably the suppositorycomprises about 2% to about 25% by weight polysorbate. The suppositorybase has a molecular weight in the range of about 400 to about 5000,preferably about 950 to about 3700. In a more preferred embodiment, thepolyethylene glycol suppository base is comprised of about 39% by weightof polyethylene glycol having a molecular weight of about (3000) andabout 59% by weight of polyethylene glycol having a molecular weight ofabout 400. A suitable commercially available polyethylene glycolsuppository base is POLYBASE, available from Paddock Laboratories, Inc.

The suppository base optionally includes either or both of apreservative(s) and a buffer(s). The preservative is selected from thegroup consisting of thimersal, benzoic acid, benzoic acid derivatives,benzylkonium, benzylkonium chloride sulfites, quaternary ammonium salts,chloro-butanol and combinations thereof at concentrations ranging fromabout 0.01% to about 0.5%. The buffers are employed so that the pH ofthe suppository vaccine remains the same. The buffers used are thoseknown in the art and include, but are not limited to citrate, phosphate,hepes (or their salts) and combinations thereof at a concentration inthe range of about 5 milimolar to about 0.5 molar.

The suppository base confers a degree of miscibleness with the mucousmembrane surfaces of the vagina or rectum, wherein suspended particlesof the vaccine and/or vaccine adjuvant(s) are in contact with suchmucous membrane surfaces for a sufficient amount of time to elicit ahumoral- or cell-mediated immune response. The suppository base has anadjuvant effect that enhances the immune response by allowing thevaccine to facilitate contact time with the vaginal or anorectal tractmucous membranes, serving as a depot that slowly releases antigen, andby localizing and delivering antigens to immunocompetent cells. Thesuppository base possesses properties that allow the suppository to bemolded in a desirable form and further function as a structuralnecessity that keeps the suppository in its desired molded form at orbelow room temperature.

The suppository is allowed to harden in a suppository shell or a moldthat forms the desired shape. The suppository is generally stored in theshell until used or is removed from the mold and repackaged. Thesuppository shell or mold is any shell or mold known in the art suitablefor molding or packaging of the suppository. A suitable commerciallyavailable laminate suppository shell is a polyvinylchloride polyethylenelaminate suppository shell available from Paddock Laboratories, Inc.

The suppository based vaccine delivery system of the present inventionis prepared by general techniques known in the art. Typically, thesuppository base vaccine delivery system is prepared under a sterileenvironment. The suppository base is heated in a sterile environment toa temperature in the range of its melting point to liquefy the base. Thesuppository base is heated for a time sufficient to liquefy it withoutdegrading it.

The vaccine or vaccine adjuvant(s) comprising the whole or fractionatedviral or other microbial pathogen, or their purified cellularconstituents or derivatives, whether native, mutated, synthetic, clonedor recombinantly expressed, that consist of nucleic acids, proteins,lipids or other antigenic determinants capable of producing humoral-orcullular-mediated immunity is placed in a container containing theliquified suppository base. The vaccine and/or vaccine adjuvant(s) arestirred with the liquid suppository base until a homogeneous suspensionis produced. A preservative or adjuvant is added and stirred until ahomogeneous suspension is again attained. The suspension comprising thesuppository base and the vaccine and/or vaccine adjuvant(s) andpreservative is placed into individual laminate suppository shells. Thesuppository is then cooled at room temperature to allow it to harden.The suppositories are then heat-sealed and stored at refrigeratedtemperature.

The suppository based vaccine delivery system according to the presentinvention when inserted into a bodily orifice and allowed to liquify orbecome water-miscible allows the vaccine to be in contact with thevaginal or rectal tract mucous membrane for a sufficient period of timeto enhance the immune response. Further, the suppository based vaccinedelivery system according to the present invention allows theincorporation of vaccine, vaccine adjuvant(s) and preservative and iseasily administered, does not require the patient to lie in a supineposition for an extended period of time after receiving the vaccination,is suitably administered by the patient, is painless, is amenable toroutine booster vaccinations and allows a favorable method of antigendelivery to immunocompetent cells through the mucosa.

The present invention is further exemplified in the following example.The example illustrates the effectiveness of the suppository basedvaccine delivery system of the present invention. It is understood thatthe example is only illustrative of preferred embodiments according tothe present invention wherein the claims set forth the scope of thepresent invention.

EXAMPLE

In this example, the HSV-2 gD2 and its complementary DNA are used asrepresentative vaccine candidates for mucosal immunization. This proteinis specific to the herpes simplex-2 (HSV-2) virus and represents a majorouter membrane constituent of the virus that is implicated in thehost-attachment phenomena. Others have demonstrated that this protein isa candidate vaccine to prevent transmission or recurrence of HSV-2. Thisis based on its antigenicity and, that following parenteral vaccination,it elicits satisfactory immune response based on protection againstHSV-2 challenge in animal models. The DNA of HSV-2 gD2 is the clonedcomplementary DNA encoding this protein. Its use as a DNA vaccine isintended to stimulate the production of cellular-mediated immuneresponse. Both the protein and cDNA is manufactured by Protein Express,Inc., Cincinnati, Ohio.

POLYBASE, a polyethylene glycol polysorbate suppository basemanufactured by and available from Paddock Laboratories, Inc., in anamount sufficient to manufacture 50 two-gram suppositories, was heatedin a sterile flask atop a magnetic stirrer/heater to a temperature ofabout 60° C. for about one hour to liquefy the suppository base.Recombinant HSV gD2 protein and/or its complementary DNA, 500 microgramseach (enough to manufacture about 50 suppositories) was asepticallyplaced in the liquefied suppository base suppository. A sterile magneticstir bar was placed in the flask, and the vaccine and suppository basewere stirred for about 10 minutes at about 60° C. in atemperature-controlled water bath to form a homogeneous suspension.Thimersal, as a preservative, was added to a final concentration ofabout 0.1% and stirred until a homogeneous suspension was achieved. Thesuspension comprised of the suppository base, the vaccine and thepreservative was then placed into individual polyvinylchloride-polyethylene laminate suppository shell using a sterilepipette. Approximately 2.0 ml of the suspension was placed into eachshell.

The suppository base was cooled at a temperature of about 24° C. forabout 30 minutes to harden the suppository base. The top of each shellwas heat-sealed and the suppositories were then stored at about 4° C.When used, the suppositories are removed from the shell and insertedvaginally or rectally.

While various embodiments of a suppository based vaccine delivery systemfor treating or prophylaxes against urogenitally and/or anorectallytransmitted or localized infectious diseases and a method for treatingor prophylaxes against urogenitally and/or anorectally transmittedinfections in humans and animals have been disclosed, it should beunderstood that modifications and adaptations thereof will occur topersons skilled in the art. Other features and aspects of this inventionwill be appreciated by those skilled in the art upon reading andcomprehending this disclosure. Such features, aspects, and variationsand modifications of the reported results and examples are clearlywithin the scope of the invention where the invention is limited solelyby the scope of the following claims.

1. A suppository based vaccine delivery system for prophylaxis againstor treatment of urogenitally and anorectally transmitted infectiousdisease in humans and animals, said suppository comprising: a. a vaccineor vaccines adjuvant(s) selected from the group consisting of whole orfractionated viral or other microbial pathogens, or their purifiedcellular constituents, whether native, mutated, synthetic, cloned orrecombinantly-expressed and combinations thereof, that consists ofnucleic acids, proteins, lipids, other antigenic determinants orcombinations thereof capable of producing humoral- or cellular-mediatedimmunity in humans or animals; and b. a suppository base, selected fromthe group consisting of polyethylene glycol, polysorbate andcombinations thereof; wherein the suppository is adapted to be insertedinto a bodily orifice of a human or animal so as to allow thesuppository to be in contact with tissue of the bodily orifice tofacilitate transfer of suppository material therethrough.
 2. Asuppository based vaccine delivery system for prophylaxis againsturogenital tract infections in humans, said suppository comprising: a. avaccine or vaccine adjuvant(s) selected from the group consisting ofwhole or fractionated viral or other microbial pathogens, or theirpurified cellular constituents, whether native, mutated, synthetic,cloned or recombinantly-expressed and combinations thereof, thatconsists of nucleic acids, proteins, lipids, other antigenicdeterminants or combinations thereof capable of producing humoral orcellular-mediated immunity in humans; and b. a suppository base,selected from the group consisting of polyethylene glycol, polysorbateand combinations thereof; Wherein the suppository is adapted to beinserted vaginally so as to allow the suppository to be in contact withvaginal mucous membrane to facilitate transfer of suppository materialtherethrough.
 3. A suppository based vaccine delivery system forprophylaxis against anorectally transmitted infectious disease in humansor animals, said suppository comprising: a. a vaccine or vaccineadjuvant(s) elected from the group consisting of whole or fractionatedviral or other microbial pathogens, or their purified cellularconstituents, whether native, mutated, synthetic, cloned orrecombinantly expressed and combinations thereof, that consists ofnucleic acids, proteins, lipids, other antigenic determinants orcombinations thereof capable of producing humoral or cellular-mediatedimmunity in humans or animals; and b. Suppository base, selected fromthe group consisting of polyethylene glycol, polysorbate andcombinations thereof; Wherein the suppository is adapted to be insertedrectally so as to allow the suppository to be in contact with theanorectal mucous membrane to facilitate transfer of vaccine or vaccineadjuvant material therethrough.
 4. The suppository based vaccinedelivery system of claim 1 wherein the vaccine content or vaccineadjuvant(s) is selected from the group consisting of whole cells,purified constituents or is generated from known genetic information ofurogenital or anorectally transmittable pathogens.
 5. The suppositorybased vaccine delivery system of claim 1 wherein the vaccine or vaccineadjuvant(s) contents are present in the total amount of 10 to 1000micrograms.
 6. The suppository based vaccine delivery system of claim 1wherein the suppository base is comprised of polyethylene glycol andpolysorbate.
 7. The suppository based vaccine delivery system of claim 6wherein the polyethylene glycol suppository base is comprised of about75% to about 98% by weight polyethylene glycol and about 2% to about 25%by weight polysorbate.
 8. The suppository based vaccine delivery systemof claim 6 wherein the polyethylene glycol has an average molecularweight of about 950 to about
 3700. 9. The suppository based vaccinedelivery system of claim 6 wherein the polyethylene glycol suppositorybase comprises from about 70% to greater than 99% by weight of thesuppository.
 10. The suppository based vaccine delivery system of claim1 wherein the suppository is further comprised of a preservativeselected from the group consisting of thimersal, benzoic acid,benzylkonium, benzylkonium chloride, sulfites, quaternary ammoniumsalts, chlorobutanol and combinations thereof.
 11. The suppository-based vaccine delivery system of claim 10 wherein the suppository isfurther comprised of an emulsifying agent selected from the groupconsisting of gelatin, methyl cellulose, alginic acid, sodium laurylsulfate and combinations thereof.